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Loss of α-catenin elicits a cholestatic response and impairs liver regeneration.
- Source :
-
Scientific reports [Sci Rep] 2014 Oct 30; Vol. 4, pp. 6835. Date of Electronic Publication: 2014 Oct 30. - Publication Year :
- 2014
-
Abstract
- The liver is unique in its capacity to regenerate after injury, during which hepatocytes actively divide and establish cell-cell contacts through cell adhesion complexes. Here, we demonstrate that the loss of α-catenin, a well-established adhesion component, dramatically disrupts liver regeneration. Using a partial hepatectomy model, we show that regenerated livers from α-catenin knockdown mice are grossly larger than control regenerated livers, with an increase in cell size and proliferation. This increased proliferation correlated with increased YAP activation, implicating α-catenin in the Hippo/YAP pathway. Additionally, α-catenin knockdown mice exhibited a phenotype reminiscent of clinical cholestasis, with drastically altered bile canaliculi, elevated levels of bile components and signs of jaundice and inflammation. The disrupted regenerative capacity is a result of actin cytoskeletal disorganisation, leading to a loss of apical microvilli, dilated lumens in the bile canaliculi, and leaky tight junctions. This study illuminates a novel, essential role for α-catenin in liver regeneration.
- Subjects :
- Actins metabolism
Adaptor Proteins, Signal Transducing metabolism
Animals
Bile Canaliculi pathology
Bile Canaliculi ultrastructure
Cell Cycle Proteins
Cell Proliferation
Cholestasis blood
Female
Hepatocytes physiology
Mice
Mice, Knockout
Microvilli ultrastructure
Models, Animal
Phosphoproteins metabolism
YAP-Signaling Proteins
alpha Catenin deficiency
Cholestasis genetics
Liver Regeneration physiology
alpha Catenin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 25355493
- Full Text :
- https://doi.org/10.1038/srep06835